Kinetic parameters of Thymidine kinase and DNA synthesis during liver regeneration: role of thyroid hormones.

The role of thyroid hormones in DNA synthesis and in the activity of Thymidine kinase (TK), a key regulatory enzyme of DNA synthesis was studied in proliferating hepatocytes in vivo. Liver regeneration after partial hepatectomy was used as a model for controlled cell division in rats having different thyroid status - euthyroid, hypothyroid and 3,3',5'-triiodo-L-thyronine (T3)-treated hypothyroid. Partial hepatectomy caused a significant elevation of DNA synthesis (p<0.01) in all the three groups compared to their sham-operated counterparts. Hypothyroid hepatectomised animals showed significantly lower (p<0.01) level of DNA synthesis than euthyroid hepatectomised animals. A single subcutaneous dose of T3 to hypothyroid sham-operated animals resulted in a significant increase (p<0.01) of DNA synthesis in the intact liver. This was comparable to the level of DNA synthesis occurring in regenerating liver of euthyroid animals. In hypothyroid hepatectomised animals, T3 showed an additive effect on DNA synthesis and this group exhibited maximum level of DNA synthesis (p<0.01). Studies of the kinetic parameters of TK show that the Michelis-Menten constant, (K(m)) of TK for thymidine was altered by the thyroid status. K(m) increased significantly (p<0.01) in untreated hypothyroid animals when compared to the euthyroid rats. T3 treatment of hypothyroid animals reversed this effect and this group showed the lowest value for K(m) (p<0.01). Thus our results indicate that thyroid hormones can influence DNA synthesis during liver regeneration and they may regulate the activity of enzymes such as Thymidine kinase which are important for DNA synthesis and hence cell division.